Venlafaxine extended release versus citalopram in patients with depression unresponsive to a selective serotonin reuptake inhibitor

Abstract

Findings from the National Institute of Mental Health's Sequenced Treatment Alternatives to Relieve Depression trial indicate that approximately 50% of patients with major depressive disorder do not experience a treatment response after adequate first-line treatment with a selective serotonin reuptake inhibitor (SSRI). This study was designed to test the hypothesis that, after treatment failure with an SSRI, switching to venlafaxine extended release (ER) would offer advantages over switching to another SSRI, citalopram. The objectives of this trial were to compare the efficacy and safety of venlafaxine ER and citalopram in the treatment of moderate-to-severe depression in patients who did not experience a treatment response to an SSRI other than citalopram and to investigate the effects of severity of depression by categorizing treatment groups according to baseline severity. This was a 12-week, double-blind, randomized, parallel-group, multicenter study. Participants were adult outpatients who, following 8 weeks of monotherapy with an adequate dosing regimen of an SSRI other than citalopram and had not responded, met the diagnostic criteria for depression as described in the Diagnostic and statistical manual of mental disorders, fourth edition, and had a score > or =20 on the 21-item Hamilton Rating Scale for Depression (HAM-D21). After a 7-day screening period, patients were randomly assigned to receive venlafaxine ER 75 mg/day or citalopram 20 mg/day for the first 2 weeks. Doses could be increased every 2 weeks through week 6. Treatment lasted 12 weeks and was followed by a 1-week tapering period. Maximum dosages were venlafaxine ER 300 mg/day or citalopram 60 mg/day. The primary end point was the final on-therapy total HAM-D21 score. To investigate the treatment effects of the severity of depression on efficacy, a subgroup analysis was performed for baseline HAM-D21 total score < or =31 and >31. The analyses for HAM-D21, Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions - Severity (CGI-S), and Clinical Global Impressions - Improvement scores were based on intent-to-treat (ITT) population, for both the primary analysis and subgroup analysis according to baseline HAM-D21 total scores < or =31 or >31. Safety assessments included the recording of adverse events (AEs). A total of 406 patients (200 venlafaxine ER, 206 citalopram) were randomly assigned and 396 patients were included in the ITT population (194 venlafaxine ER, 202 citalopram). Treatment groups were similar in terms of demographics and baseline psychiatric assessments. Two hundred and eighty-four patients (137 venlafaxine ER, 147 citalopram) were present in the ITT population with a baseline HAM-D21 total score < or =31 and 112 patients (57 venlafaxine ER, 55 citalopram) in the >31 group. In the primary analysis, there was no statistical difference between groups. The group with a baseline HAM-D21 total score of 20-31 did not differ significantly in any efficacy parameters. In the group with a baseline HAM-D21 total score ...

The Integrative Management of Treatment-Resistant Depression: A Comprehensive Review and Perspectives

“…After 4 weeks of either paroxetine or venlafaxine, the venlafaxine group demonstrated a remission rate of 37% compared with the remission rate of 18% in the paroxetine group (p = 0.01). The second double-blind study followed 406 patients who failed to respond to ongoing SSRI treatment [37]. Unlike the prior trial, this study demonstrated no advantage of venlafaxine XR with regard to the primary outcome measure, in this case the HDRS-21.…”

Consider augmentation or switching strategies when first-line antidepressants are unsuccessful in major depressive disorder

“…In four RCTs in SSRI nonresponders, [3,[9][10][11] a significant benefit with regard to response [11] and/or remission [9,11] was shown in pts switched to venlafaxine vs a second SSRI in two trials Overall, venlafaxine appears to be an effective and useful agent after the failure of an SSRI, but whether it is markedly more effective than other options seems doubtful Switching to a newer SNRI Studies are needed to determine the role of newer SNRIs in treatment-resistant MDD, as no available RCTs have investigated switching to newer SNRIs (e.g. duloxetine, desvenlafaxine and milnacipran) in treatment-resistant pts…”

Publication Bias and the Efficacy of Antidepressants

“…An example of an equivocal trial would be an active control equivalence trial, or non-inferiority trial, in which a new drug is compared to a known effective drug, in the absence of a placebo control (7)(8)(9). An example of an equivocal trial would be an active control equivalence trial, or non-inferiority trial, in which a new drug is compared to a known effective drug, in the absence of a placebo control (7)(8)(9).…”